title: Design, synthesis and biological evaluation of rose bengal analogues as SecA inhibitors.
abstract: SecA, a key component of bacterial Sec-dependent secretion pathway, is an attractive target for exploring novel antimicrobials. Rose bengal (RB), a polyhalogenated fluorescein derivative, was found from our previous study as a potent SecA inhibitor. Here we describe the synthesis and structure-activity relationships (SAR) of 23 RB analogues that were designed by systematical dissection of RB. Evaluation of these analogues allowed us to establish an initial SAR in SecA inhibition. The antimicrobial effects of these SecA inhibitors are confirmed in experiments using E. coli and B. subtilis.
authors.affiliation: Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, P.O. Box 4098, Atlanta, GA 30302-4098, USA.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Cui
authors.forename: Jinshan
authors.initials: J
authors.lastname: Jin
authors.forename: Ying-Hsin
authors.initials: YH
authors.lastname: Hsieh
authors.forename: Hsiuchin
authors.initials: H
authors.lastname: Yang
authors.forename: Bowen
authors.initials: B
authors.lastname: Ke
authors.forename: Krishna
authors.initials: K
authors.lastname: Damera
authors.forename: Phang C
authors.initials: PC
authors.lastname: Tai
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D026901:Membrane Transport Proteins / Q000378:metabolism; D011485:Protein Binding; D012395:Rose Bengal / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000069816:SEC Translocation Channels; D000081416:SecA Proteins; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D026901:Membrane Transport Proteins; D000069816:SEC Translocation Channels; D012395:Rose Bengal; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins
keywords: SecA inhibitors; antimicrobial agents; drug discovery; rose bengal analogues; structure-activity relationships